Prognostic value of nucleotyping, DNA ploidy and stroma in high-risk stage II colon cancer

Lujing Yang,Li Zhang,Lixin Zhou,Aiwen Wu,Zhongwu Li,Pengju Chen,Tingting Sun,Lin Wang

doi:10.1038/s41416-020-0974-8

Lujing Yang, Li Zhang + Show 6 more

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https://doi.org/10.1038/s41416-020-0974-8

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Abstract

BackgroundHeterogeneity with respect to recurrence and survival in high-risk stage II colon cancer patients still exists, and further classification is urgently required. This study aimed to ascertain the prognostic value of DNA ploidy, stroma-tumour fraction and nucleotyping in the prognosis of high-risk stage II colon cancer.MethodsA total of 188 high-risk stage II colon cancer patients received radical surgery in Peking University Cancer Hospital, from 2009 to 2015. Status of mismatch repair proteins in tumours was analysed using immunohistochemistry. DNA ploidy, stroma-tumour fraction and nucleotyping were estimated by automated digital imaging systems.ResultsNucleotyping and DNA ploidy were significant prognostic factors, while stroma-tumour fraction were not significantly prognostic in the univariate analysis. In the multivariable model, the dominant contributory factor of disease-free survival was chromatin heterogeneous vs. chromatin homogeneous [HR 3.309 (95% CI: 1.668–6.564), P = 0.001].ConclusionsOur study indicates that nucleotyping is an independent prognostic factor in high-risk stage II colon cancer. Therefore, it may help subdivide patients into different subgroups and give them different strategies for follow-up and treatment in the future.

Highlights

Heterogeneity with respect to recurrence and survival in high-risk stage II colon cancer patients still exists, and further classification is urgently required
A positive correlation between pathological T-stage and stromatumour fraction was observed in our cohort, which meant that the higher the pathological T-stage, the more the tumour stroma
A previous study has shown that chemotherapy improves survival in stage II colorectal cancer, the absolute improvements are only 3.6%

Summary

Introduction

Heterogeneity with respect to recurrence and survival in high-risk stage II colon cancer patients still exists, and further classification is urgently required. This study aimed to ascertain the prognostic value of DNA ploidy, stroma-tumour fraction and nucleotyping in the prognosis of high-risk stage II colon cancer. RESULTS: Nucleotyping and DNA ploidy were significant prognostic factors, while stroma-tumour fraction were not significantly prognostic in the univariate analysis. CONCLUSIONS: Our study indicates that nucleotyping is an independent prognostic factor in high-risk stage II colon cancer. It may help subdivide patients into different subgroups and give them different strategies for follow-up and treatment in the future. This and replication stress may contribute to CIN.[11,12] DNA aneuploidy or tetraploidy is an accepted marker of CIN that has been shown to be associated with poor prognosis in CRC.[13,14,15] In addition, other studies have shown that CIN-associated cancers exhibit enhanced invasiveness, which may increase the likelihood of metastasis of CRC.[16]

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